Dioxathiocin carboxylic acids, esters, salts and amides

ABSTRACT

Novel dioxathiocin carboxylic acids, esters, salts and amides, which reduce blood lipids in warm blooded animals, are useful in the treatment of hyperlipidemic states and possess anti-infective properties, are represented by compounds of the following formula: WHEREIN EACH Y, Y&#39;&#39;, Z and Z&#39;&#39; represent hydrogen, halogen such as chlorine, fluorine, bromine or iodine, or lower alkyl or from one to four carbon atoms; or each set of Y and Y&#39;&#39; or each set of Z and Z&#39;&#39; forms a napthalene ring which may be unsubstituted or substituted with a substituent selected from a halogen atom such as chlorine, fluorine, bromine or iodine or lower alkyl of from one to four carbon atoms; W represents hydroxy, lower alkoxy of from one to four carbon atoms; or -NR1R2; R1 and R2 represent hydrogen or lower alkyl of from 1 to 4 carbon atoms and may be the same or different; or R1 and R2 taken together with the nitrogen atom to which each is attached form a saturated monocyclic heterocyclic group such as pyrrolidino, piperidino, morpholino, piperazino or N-(lower)-alkyl-piperazino.

United States Patent 1 i Parker 1 1 Jan.30, 1973 [541 DIOXATHIOCIN CARBOXYLIC ACIDS,

ESTERS, SALTS AND AMIDES [75] Inventor: Roger Alan Parker, Cincinnati,

Ohio

[73] Assignee: Richardson Merre1lInc.,New York,

[22] Filed: Sept. 13, 1971 21 Appl. No.: 180,117

[5 6] References Cited OTHER PUBLICATIONS Adams, Chemical Abstracts, 5321213 (1-1959) Primary Examiner-Henry R. .liles Assistant ExaminerCecilia M. S. Jaisle Attorney-Eugene O. Retter et al.

[57] ABSTRACT Novel dioxathiocin carboxylic acids, esters, salts and amides, which reduce blood lipids in warm blooded animals, are useful in the treatment of hyperlipidemic states and possess anti-infective properties, are represented by compounds of the following formula:

Formula I wherein each Y, Y, Z and Z represent hydrogen, halogen such as chlorine, fluorine, bromine or iodine,

, or lower alkyl or from one to four carbon atomsgor each set of Y and Y' or each set of Z and Z forms a napthalene ring which may be, unsubstituted or substituted with a substituent selected from a halogen atom such as chlorine, fluorine, bromine or iodine or lower alkyl of from one to four carbon atoms; W represents hydroxy, lower alkoxy of from one to four carbon atoms; or NRR R and R represent hydrogen or lower alkyl of from 1 to 4 carbon atoms and may be the same or different; or R and R taken together with the nitrogen atom to which each is attached form a saturated monocyclic heterocyclic group such as pyrrolidino, piperidino, morpholino, piperazino or N-(lower)-alkyl-piperazino.

14 Claims, N0 Drawings DIOXATI-IIOCIN CARBOXYLIC ACIDS, ESTERS; SALTS AND AMIDES FIELD OF INVENTION 7 This invention relates to novel dibenzo[d,g][ 1,3,61dioxathiocin, dinaphtho[2,l-d:l, 2-g][l,3,6]di oxathiocin, and dinaphtho[ l ,2-d:-2',1 -g][ I,3,6]dioxathiocin carboxylic acids, esters, salts, and amides which reduce blood lipids in warm blooded animals, are useful in the treatment of hyperlipidemic states and possess anti-infective properties.

SUMMARY OF THE INVENTION The novel compounds of this invention are l5 represented by the following formula,

i l cH-b-W ,z' -0 Formula I wherein each Y, Y, Z and Z represents hydrogen, halogen such as chlorine, fluorine, bromine or iodine, or lower alkyl of from one to four carbon atoms; or each set of Y and Y or each set of Z and 2' taken together with the aromatic ring to which each is attached forms a naphthalene ring which may be unsubstituted or substituted with a substituent selected from a halogen atom such as chlorine, fluorine, bromine or iodine or lower alkyl of from one to four carbon atoms; W represents hydroxy or lower alkoxy of from one to four carbon atoms or -NRR R and R represent hydrogen or lower alkyl of from one to four carbon atoms and may be the same or different; or R and R taken together with the nitrogen atom to which each is attached form a saturated monocyclic heterocyclic group such as 'pyrrolidino, piperidino, morpholino, piperazino or N-(lower)-alkyl-piperazino.

As can be seen from the above Formula I compounds of this invention can be dibenzo[d,g][l,3,6]dioxathio cin derivatives as represented by the following Formula Formula II 12 11 Formula 111 I 168 8 H-(l-W 59 mi 14 v 12 R Formula IV In the above Formulas II, III, and IV each of Z, Z, Y, Y and R represent hydrogen, halogen such as chlorine, fluorine, bromine or iodine, or lower alkyl of from one to four carbon atoms and W has the meaning defined hereinbefore.

DETAILED DESCRIPTION OF INVENTION The most preferred compounds of this invention are represented by the following Formulas V and VI:

Formula V Formula VI As examples of compounds of this invention there may be mentioned, for example,

2,l-dichlorodibenzo[d,g][1,3,6]dioxathiocin-6- carboxylic acid, dinaphtho[2,l-d:l,2-g][1,3,6]dioxathiocin-8-carboxylic acid, 2,4,8,]O-tetrachlorodibenzo[d,g,][1,3 ,6]dioxathiocin-6--carboxylic acid, methyl dioxathiocin-6carboxylate, 2,4,8,10-tetrachloroclibenzo[d,g,][ 1,3,61dioxathiocin carboxamide, ethyl 2,14-dimethyldinaphtho[2,l-d:1,2'-g]dioxathiocin-8-carboxylate, 4,12-dibromodinaphtho[2,l-d:l ',2'-g]dioxathiocin- 8-carboxamide,

3,13-diethyldinaphtho[2,l-dzl ,2'-g]dioxathiocin-8- carboxylic acid, 2,10-dichlorodinaphtho[1,2-d:2,l'-g]dioxathiocin- 8-carboxylic acid,

N,N-diethyl-5,l l-dipropyldinaphtho[2, l -d:l ',2'-

g]dioxathiocin-8-carboxamidc, 2,l-4-difluoro-N,N-dipropyldibenzo[d,g][1,3,61dioxathiocin-tS-carboxamide,

3,9-diethyldibenzo[d,g][ l ,3,6]dioxathiocin-6-carboxylic acid,

ethyl 2,4,8,l0-tetrapropyldibenzo[d,g,][ l,3,6]dioxathiocin-6-carboxylate, l,l1N,N-tetramethyldibenzo[d,g][l,3,6]dioxathiocin-6-carboxamide, 1-(dibenzo[d,g,][1,3,6]dioxathiocin-6-carbonyl)piperidine,

l-(2,10-dimethyldibenzo[d,g][ l ,3,6]dioxathiocin-6- carbonyl)pyrrolidine,

l-(2, l O-dichlorodibenzo[d,g,][ l ,3,6]dioxathiocin-6- carbonyl)piperazine, l-(2,10-dichlorodibenzo[d,g][ l ,3,6]dioxathiocin-6- carbonyl)-4propylpiperazine, 1-(2,lO-dipropylidibenzo[d,g][1,3 ,6 ]dioxathiocin-6- carbonyl)morpho1ine, and the like.

The novel compounds of this invention reduce blood lipids, particularly lipoproteins containing cholesterol and triglycerides in warm-blooded animals and are useful in thetreatment of hyperlipidemic states such as are encountered in patients with cardiovascular diseases, especially atherosclerotic diseases that can result in heart failure and stroke. Also, the compounds of this invention possess anti-infective properties.

The compounds of this invention can be used in th form'of pharmaceutical preparations which contain the novel compound suitable for oral or parenteral administration. The quantity of compound in unit dosage form can vary a wide range to provide from about 0.5 mg/kg'to about 4 g/kg of body weight and preferably 1 mg/kg to 1 g/kg of body weight of the subject per day to achieve the desired effect.

To illustrate the utility of the compounds of this invention young male rats of the Wistar strain weighing initially about 170 grams were given free access to a diet to which the indicated amount of test compound was added. This diet was prepared by thoroughly mixing the compound with commercial PURlNA CHOW (Trademark of Ralston Purina Company, St. Louis, Miss.). .Groups of animals were given these diets for a period of 10 days. Control groups were given the same diet with no added drug. At the end of the treatment 2,4,8,l0-tetrachlorodibenzo[d,g,][1,3,6]

period, all rats were bled by cardiac puncture and the plasma was analyzed for cholesterol and triglyceride content on a Technicon AUTOANALYZER (*Trademark of Technicon Corporation, Tarrytown, N.Y. 10591.). The results are given in the following Table 1.

(a) Determined by measuring food consumption. b) Compared to untreated control rats in the same experiment.

Other compounds of this invention show comparable results when administered under similar conditions.

As antiinfectives, compounds of this invention when administered subcutaneously havebeen found to be effective in mice against certain types of viruses,'for-example, encephalomyocarditis; bacteria, for example Staphylococcus aureus and Salmonella schottmuelleri; and fungi, for example, Candida albicans.

The compounds of this invention are prepared be reacting one equivalent of a compound of the formula Formula VII or a salt thereof and at least two equivalents of dihaloacetate salt, for example, dichloroacetate salt, in a suitable solvent and in the presence of excess base to give dioxathiocin carboxylate salts of Formula VII];

I g I (Bu-(mo ma Formula VIII The various symbols, Y, Y, Z and Z in the above Formulas VII and VIII have the meaning defined as in Formula l, and M represents an inorganic salt forming radical.

Although the two or more equivalents of the dihaloacetate salt reactant can all be added at the start of the reaction, it is preferred that one equivalent of the dihaloacetate salt reactant is placed in the reaction mixture initially, and then at a period of from about to 48 hours from the start of the reaction one or more equivalents of the dihaloacetate salt is added to the reaction mixture.

The salts of the thio-bisphenol or thio-bis-naphthol reactant and dihaloacetic acid are prepared in situ by addition of base. A variety of bases can be used such as, for example, potassium carbonate, sodium methoxide, potassium tert-butoxide, sodium hydroxide or potassium hydroxide. The preferred base is potassium carbonate, however, when substituted thio-bisphenols which have weaker acid values are used, it may be necessary to use a stronger base such as sodium methoxide or potassium tert-butoxide.

As examples of solvents suitable for use in the reaction there may be mentioned, for example, ethanol, npropanol, isopropanol, n-butanol, tert-butanol, dimethylformamide, dimethylsulfoxide, water and the like. The preferred solvents are n-propanol and isopropanol.

The reaction mixture is heated to reflux with vigorous stirring for 10 to 120 hours, preferably 98 hours, after which the solvent is distilled off and replaced with water. The mixture is cooled and the product, a compound of Formula VIII, is collected, which may be converted to the acid by suspending it in water and acidifying the mixture with, for example, hydrochloric acid. The precipitate is collected and recrystallized from, for example, toluene or acetic acid to give the dibenzo [d,g][l,3,6]dioxathiocin-6-carboxylic acids, that is, compounds of Formula I] wherein W represents hydroxy, and the dinaphtho[2,l-d:l,2'-g] [1,3,61dioxathiocin-8-carboxylic acids, that is, compounds of Formulas 111 wherein W represents hydroxy, or dinaphtho[ 1 ,2-d:2',l '-g][ l ,3,6]dioxathiocin-8-carboxylic acids, that is, compounds of Formula 1V wherein W is hydroxy.

The corresponding lower alkyl esters may be prepared by esterification of the above mentioned acids with lower aliphatic alcohols by generally known esterification procedures.

The corresponding dioxathiocin carboxamides may be obtained by the action of ammonia, or an appropriate primary amine such as ethylamine or propylamine, or an appropriate secondary amine such as dimethylamine, diethylamine, piperidine, morpholine, N-methylpiperazine and the like, on the acid halide or the ester of the above mentioned dioxathiocin carboxylic acids. The ester derivative may be obtained by the procedure described hereinbefore, and the acid halide may be obtained by reacting the dioxathiocin carboxylic acid with thionyl halide, for example, thionyl chloride by generally known procedures.

The reactant thiobisphenols and thiobisnaphthols, that is, compounds of Formula VII are prepared by reacting, 2 moles of an appropriately substituted phenol or naphthol with 1 mole of sulfur dichloride in the presence of a Lewis acid and under conditions generally employed for a Friedel-Crafts reaction.

EXAMPLES Representative compounds of the invention and their preparation are illustrated in the following specific examples.

EXAMPLE 1 2,4,8,10-Tetrachlorodibenzo[d,g][ l ,3,6]dioxathiocin- 6-carboxylic acid 50 g (0.141 mole) of 2,2-thiobis(4,6- dichlorophenol), 36.2 g (0.282 mole) ofpotassium carbonate, 5.0 g (0.03 mole) of potassium iodide, 18.2 g (0.141 mole) of dichloroacetic acid and 500 ml of npropanol were combined and refluxed with vigorous stirring for 48 hours after which 36.2 g (0.282 mole) of potassium carbonate and 18.2 g (0.141 mole) of dichloroacetic acid were added. The mixture was refluxed with stirring an additional 24 hours, then the solvent was removed by distillation being gradually replaced with water. The mixture was allowed to cool, and the precipitate was collected and washed with 500 ml of 2 percent aqueous potassium hydroxide. The solid was suspended in 1 liter of water to which was added hydrochloric acid until the mixture was acidic to litmus paper. The resulting solid was washed washed with water, dried and recrystallized twice from toluene to give 24 g of the desired product, M.P. 231-233C (dec.).

EXAMPLE 2 Methyl 2,4,8,10-tetrachlorodibenzo[d,g][1 ,3,6] dioxathiocin-6-carboxylate To 500 ml of methanol containing 5 ml of concentrated sulfuric acid was added 20.0 g (0.05 mole) of 2,4,8, 1 0-tetrachlorodibenzo[d,g][ l ,3 ,6]dio'xathiocin- 6-carboxylic acid, and the mixture was refluxed for 3 hours. Upon cooling the resulting crystalline product was recrystallized from acetone-methanol to give 16.8 g of the desired product, M.P. l54-l 56C.

EXAMPLE 3 Dinaphtho[2,1-d:l ',2'-g] 1 ,3,6]dioxathiocin-8- carboxylic acid A mixture of 50.0 g (0.157 mole) of 1,l-thiodi-B- naphthol, 87.0 g (0.628 mole) of potassium carbonate, 5.0 g (0.03 mole) of potassium iodide, 20.3 g (0.157 mole) of dichloroacetic acid and 600 ml of n-propanol was refluxed with vigorous stirring for 24 hours after which an additional 20.3 g (0.157 mole) of dichloroacetic acid was added. The mixture was refluxed with stirring an additional 64 hours, then the solvent was distilled off being gradually replaced with water. The mixture was colled and the resulting precipitate was dried and recrystallized twice from toluene to give the desired product, M.P. 233238C (dec.).

EXAMPLE 4 2,10-Dichlorodibenzo[d,g][ 1,3 ,6]dioxathiocin-6- carboxylic acid Substituting an appropriate amount of 2,2'-thiobis(4 5 1| -chlorophenol) for 2,2-thiobis(4,6-dichlorophenol) in the procedure of Example 1, the desired product was obtained, M.P. 224-227C.

EXAMPLE 5 Methyl 2,10-dichlorodibenzo[d,g][ l ,3,6]dioxathiocin- 6-carboxylate Substituting 2,10-dichlorodibenzo[d,g][ l ,3,6]dioxathiocin-6-carboxylic acid for 2,4,8, 1 O- tetrachlorodibenzo[d,g,[ l,3,6ldioxathiocin--carboxylic acid in the procedure of Example 2, the desired product was obtained, M.P. l96l98C.

EXAMPLE 6 n-Propyl2,4,8,lO-tetrachlorodibenzo[d,g,][1,3,6] dioxathiocin-o-carboxylate By the procedure of Example 2 only substituting npropanol for methanol the desired product is obtained.

EXAMPLE 7 2,4,8,lO-Tetrachlorodibenzo[d,g][ l ,3,6]dioxathiocin- -carboxamide A mixture of 2,4,8,lO-tetrachlorodibenzo[d,g,] [l,3,6]dioxathiocin-6-carboxylic acid and excess thionyl chloride is refluxed for 2 hours'after which the thionyl chloride is removed by distillation under reduced pressure affording the acid chloride. This acid chloride is slowly added to an excessof cold strong ammonia with stirring. The temperature of the reaction is kept below C with an ice bath. The reaction mixture is diluted with water and the resulting precipitate collected to give the desired product.

EXAMPLE 8 By the procedure of Example 7, only substituting for ammonia, approximately a l0 fold excess of diethylamine, piperidine, morpholine, or N-methylpiperazine dissolved in approximately a two fold volume of water the following compounds are obtained:

N,N-diethyl-2,4,8,lO-tetrachlorodibenzo[d,g,

l ,3,6]dioxathiocin-6-carboxamide, l-(2,4,8,l O-tetrachlorodibenzo[d,g,][ l ,3,6]dioxathiocin-fi-carbonyl)-piperidine, l-(2,4,8,lO-tetrachlorodibenzo[d,g,][1,3,6]dioxathiocin-o-carbonyl)-morpholine,

l-(2,4 ,8, l O-tetrachlorodibenzo[d,g,][ l ,3,6]dioxathiocin--carbonyl)-4-methylpiperazine By the procedureof Example I only substituting for 2,2-thiobis-(4,6dichlorophenol) an appropriate amount of the phenolslisted in Table 2 the respective products listed in Table 2 are obtained.

TABLE 2 Example No. Phenol Product 9 2,2'-thiodiphenol dibenzo[d,g,][ l,3,6]di

oxathiocin-6- carboxylic acid 2,10-difluorodibenzo 8,l-[ l l oxathiocin-ocarboxylic acid dibromodibenzo[d,g,d l-[ ldioxathiocin-t'acarboxylic acid l ,2,4,8,l0,l l-hex amethyldibenzo[d,g,][ l ,3,6] dioxathiocin-6- carboxylic acid l,2,3,4,8,9,l0,l loctachlorodibenzo[d ,gJl i l oxathiocin-6- carboxylic acid l,2,4,8,l0,l l-hexachlor0dibenzo[d,g,]

[1,3,6]di oxathiocin-6 carboxylic acid.

2,2'-thiobis(4-fluorophenol) 2,2'-thiobis(4-bromophenol) 6,6'-thiodipseudocumenol l3 2,2'-thiobis(tetrachlorophenol) 2,2'-thiobis(3,4,6-trichlorophenol) By the procedure of Example 3 only substituting for l,l-thiodi-B-naphthol an appropriate amount of the naphthols listed in Table 3 the respective products listed in Table 3 are obtained.

2,10-Dimethyldibenzo[d,g][ l ,3 ,6]dioxathiocin-6- carboxylic acid By the procedure of Example I only substituting for 2,2-thiobis(4,6-dichlorophenol) an appropriate amount of 2,2'-thiodi-p-cresol, the desired product was obtained, M.P. l9820l (dec.).

EXAMPLE 20 Methyl 2, l 0-dimethyldibenzo[d,g][ l ,3,6]dioxathiocin- 6-carboxylate By the procedure of Example 2, only substituting for 2,4,8, 1 O-tetrachlorodibenzo[d,g][ l ,3,6]dioxathiocin- 6-carboxylic acid, an appropriate amount of 2,10-

dimethyldibenzo[d,g]fc[ l ,3,6]dioxathiocin--carboxylic acid the desired compound was obtained, M.P. 104-106C.

EXAMPLEZI By the procedure of Example 7 only substituting for 2,4,8 ,10-tetrachlorodibenzo[d,g]l l ,3,6]dioxathiocin- -carboxylic acid appropriate amounts of l,2,4,8,l0,l 1-hexamethyldibenzo[d,g][1,3,61dioxathiocin-6-carboxylic acid, dibenzo[d,g][l,3,6]dioxathiocin-6-carboxylic acid and dinaphtho[2,l-d:l',2'- g][l,3,6]dioxathiocin-8-carboxylic acid and substituting excess dipropylamine, dissolved in a two fold volume of water, for ammonia the following compounds are obtained:

N,N-dipropyl-l ,2,4,8,l0,1 l-hexamethyldibenzo[d,g

][l,3,6]dioxathiocin-6-carboxylic acid N,N-dipropyldibenzo[d,g]1,3 ,6ldioxathiocin-6-carboxamide,

N,N-dipropyldinaphtho[2, l -d:l ',2'-g]ll,3,6]dioxathiocin-8-carboxamide.

I claim:

1. A compound of the formula wherein each of Y,Y, Z, and Z is selected from the group consisting of hydrogen, halogen, or a lower alkyl radical of from one to four carbon atoms; or each set of Y and Y or each set of Z and Z taken together with the aromatic ring to which each set is attached forms a naphthalene ring which may be unsubstituted or substituted with a substituent selected from a halogen atom, or a lower alkyl radical of from one to four carbon atoms; W is selected from the group consisting of hydroxy, a lower alkoxy radical of from one to four carbon atoms or NR'R wherein each of R and R is selected from the group consisting of hydrogen or a lower alkyl radical of from one to four carbon atoms, or R and R taken together with the nitrogen atom to which each is attached form a saturated monocyclic heterocyclic group selected from pyrrolidino, piperidino, morpholino, piperazino, or N-(lower)-alkylpiperazino.

2. A compound of claim 1 wherein W is selected from hydroxy or a lower alkoxy radical of from one to four carbon atoms.

3. A compound of claim 2 wherein each of Y, Y, Z, and Z is selected from hydrogen, halogen or a lower alkyl radical of from one to four carbon atoms.

4. A compound of claim 3 which is 2,10-dimethyldibenzo[d,g][ l ,3,6]dioxathiocin-o-carboxylic acid.

5. A compound of claim 3 which is methyl 2, l 0dimethyldibenzo-[d,g][ l ,3,6]dioxathiocin-6-carboxylate.

6. A compound of claim 3 wherein each of Y, Y, Z, and Z is selected from hydrogen or chlorine.

7 A compound of claim 6 which is carboxylic acid.

8. A compound of claim 6 which is methyl 2,4,8,l0- tetrachlorodibenzo[d,g][ l,3,6]dioxathiocin-6-carboxylate.

9. A compound of claim 6 which is 2,10-

diclorodibenzo[d,g]e[ 1,3,6 ]dioxathiocin--carboxylic acid.-

10. A compound of claim 6 which is methyl 2,10- dichlorodibenzo[d,g]ey[ l,3,6]dioxathiocin-6-carboxylate.

11. A compound of claim 1 wherein each set of Z and Z taken together with the aromatic ring to which each set is attached form a naphthalene ring which may be unsubstituted or substituted with a halogen atom, or a lower alkyl radical of from one to four carbon atoms.

12. A compound of claim 11 wherein W is selected from hydroxy or a lower alkoxy of from one to four carbon atoms.

13. A compound of claim 12 which is dinaphtho[2,ld: l ',2-g][ l ,3,61dioxathiocin-8-carboxylic acid.

14. A compound of claim 1 wherein each set of Y and Y taken together with the aromatic ring to which each set is attached forms a naphthalene ring which may be unsubstituted or substituted with a halogen atom, or a lower alkyl radical of from one to four carbon atoms.

UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent No. 3 '71 L 1 Q'l Dated January 30 I Q7? Inven Rngnrma Parker It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

In the Abstract of line 5,- after formula 1, the second occurence of "or" should read -of-.

Signed and Sealed this thirt Day of January 1976 [SEAL] A ttes t."

RUTH C. MASON C. MARSHALL DANN Arresting Officer Commissioner ofPaIenls and Trademarks UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT NO. 1 3 714 1 1 DATED 1 January 50, 1973 INVENTOR(S) Roger Alan Parker It is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below: I n the Abstract at Line 3 after Formula second occurence of "or" should read "of" Li ne l after Formula I through I ine 5 "each set of or sub-" should read "each set of Z and 2' taken together wi th the aromatic ring to which each is attached Forms a naphthalene ring which may be unsubstituted or substituted" Column 1,

Y' Yr 3 s Formula II should read @z- Column 5, l ine 54 Form can vary a wide range" should read "Form can var over a wide range".

Column "I, Table I at l ine 7 add 'Dai ly Dose" above columns 2 and 5; line 36 "be" should read "by"; Formula VIII CH-COO-M should read cH-coo'M. Column 6, line 31 -O/ "col led" should read "cooled". Column 8, l ine 6 "[d,g,d" should read [d,g]"; l ine 66 [d,g]fc" should read [d, g] Q Column 10, l ine 27 [d,g]e' should read [d,g]" l ine 5O [d,g]ey" should read "[d,g]".

Signed and Scaled this 0 second Day of December 1975 [SEAL] Arrest:

Q RUTH C. MASON C. MARSHALL DANN Arresting Offirer Commissioner oflarenls and Trademarks 

1. A compound of the formula
 2. A compound of claim 1 wherein W is selected from hydroxy or a lower alkoxy radical of from one to four carbon atoms.
 3. A compound of claim 2 wherein each of Y, Y'', Z, and Z'' is selected from hydrogen, halogen or a lower alkyl radical of from one to four carbon atoms.
 4. A compound of claim 3 which is 2,10-dimethyldibenzo(d,g) (1, 3,6)dioxathiocin-6-carboxylic acid.
 5. A compound of claim 3 which is methyl 2,10dimethyldibenzo-(d, g) (1,3,6)dioxathiocin-6-carboxylate.
 6. A compound of claim 3 wherein each of Y, Y'', Z, and Z'' is selected from hydrogen or chlorine.
 7. A compound of claim 6 which is 2,4,8,10tetrachlorodibenzo(d, g) (1,3,6)dioxathiocin-6-carboxylic acid.
 8. A compound of claim 6 which is methyl 2,4,8,10-tetrachlorodibenzo(d,g) (1,3,6)dioxathiocin-6-carboxylate.
 9. A compound of claim 6 which is 2,10-diclorodibenzo(d,g) (1,3, 6)dioxathiocin-6-carboxylic acid.
 10. A compound of claim 6 which is methyl 2,10-dichlorodibenzo(d,g) (1,3,6)dioxathiocin-6-carboxylate.
 11. A compound of claim 1 wherein each set of Z and Z'' taken together with the aromatic ring to which each set is attached form a naphthalene ring which may be unsubstituted or substituted with a halogen atom, or a lower alkyl radical of from one to four carbon atoms.
 12. A compound of claim 11 wherein W is selected from hydroxy or a lower alkoxy of from one to four carbon atoms.
 13. A compound of claim 12 which is dinaphtho(2,1-d:1'',2''-g) (1, 3,6)dioxathiocin-8-carboxylic acid. 